tbuckley/cabot-search huggingface dataset:
Fungal infections and the fungal microbiome in hepatobiliary disorders
Authors: Phillipp Hartmann, Bernd Schnabl
Journal: Journal of Hepatology (2022)

Liver and biliary diseases affect more than a billion people worldwide, with high associated morbidity and mortality. The impact of the intestinal bacterial microbiome on liver diseases has been well established. However, the fungal microbiome, or mycobiome, has been overlooked for a long time. Recently, several studies have shed light on the role of the mycobiome in the development and progression of hepatobiliary diseases. In particular, the fungal genus Candida has been found to be involved in the pathogenesis of multiple hepatobiliary conditions. Herein, we compare colonisation and infection, describe mycobiome findings in the healthy state and across the various hepatobiliary conditions, and point toward communalities. We detail how quantitation of immune responses to fungal antigens can be employed to predict disease severity, e.g. using antibodies to Saccharomyces cerevisiae or specific anti-Candida albicans antibodies. We also show how fungal products (e.g. beta-glucans, candidalysin) activate the host's immune system to exacerbate liver and biliary diseases. Finally, we describe how the gut mycobiome can be modulated to ameliorate hepatobiliary conditions.
CHD4 promotes acquired chemoresistance and tumor progression by activating the MEK/ERK axis
Authors: Jing Wu, Zhijun Zhou, Jin Li, Huifang Liu, Huaqi Zhang, Junchang Zhang, Weibin Huang, Yulong He, Shiyu Zhu, Mingyu Huo, Mingyang Liu, Changhua Zhang
Journal: Drug Resistance Updates (2022)

Chemoresistance remains a major challenge in gastric cancer (GC). Chromodomain helicase DNA-binding protein 4 (CHD4) mediated chromatin remodeling plays critical roles in various tumor types, but its role in chemoresistance in GC remains uncharacterized. CHD4 expression was examined by immunohistochemistry and Western blotting. The role of CHD4 on cell proliferation and chemoresistance of GC was examined in vitro and in vivo. Immunoprecipitation and liquid chromatography-mass spectrometry were used to identify CHD4-binding proteins and a proximity ligation assay was used to explore protein-protein interaction. Chemoresistance is associated with upregulation of CHD4 in the tumor tissues of GC patients. Overexpression of CHD4 increased chemoresistance and cell proliferation. Knockdown of CHD4 induced cell apoptosis and cell cycle arrest. CHD4 mediates the decrease of the intracellular concentration of cisplatin by inducing drug efflux. Additionally, CHD4 promotes the interaction between ERK1/2 and MEK1/2, resulting in continuous activation of MEK/ERK pathway. Knockdown of CHD4 in GC increased sensitivity to chemotherapy and suppressed tumor growth in a mouse xenograft model. This study identifies CHD4 dominated multi-drug efflux as a promising therapeutic target for overcoming acquired chemoresistance in GC.
Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans
Authors: Dewei Ye, Jiating Huang, Jiaming Wu, Kang Xie, Xiang Gao, Kaixuan Yan, Pengfei Zhang, Ying Tao, Yun Li, Shufei Zang, Xianglu Rong, Jun Li, Jiao Guo
Journal: Gut Microbes (2022)

Gestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.
Immunogenicity and risks associated with impaired immune responses following SARS-CoV-2 vaccination and booster in hematologic malignancy patients: an updated meta-analysis
Authors: Noppacharn Uaprasert, Palada Pitakkitnukun, Nuanrat Tangcheewinsirikul, Thita Chiasakul, Ponlapat Rojnuckarin
Journal: Blood Cancer Journal (2022)

Patients with hematologic malignancies (HM) have demonstrated impaired immune responses following SARS-CoV-2 vaccination. Factors associated with poor immunogenicity remain largely undetermined. A literature search was conducted using PubMed, EMBASE, Cochrane, and medRxiv databases to identify studies that reported humoral or cellular immune responses (CIR) following complete SARS-CoV-2 vaccination. The primary aim was to estimate the seroconversion rate (SR) following complete SARS-CoV-2 vaccination across various subtypes of HM diseases and treatments. The secondary aims were to determine the rates of development of neutralizing antibodies (NAb) and CIR following complete vaccination and SR following booster doses. A total of 170 studies were included for qualitative and quantitative analysis of primary and secondary outcomes. A meta-analysis of 150 studies including 20,922 HM patients revealed a pooled SR following SARS-CoV-2 vaccination of 67.7% (95% confidence interval [CI], 64.8-70.4%; I
Randomization, design and analysis for interdependency in aging research: no person or mouse is an island
Authors: Daniella E. Chusyd, Steven N. Austad, Stephanie L. Dickinson, Keisuke Ejima, Gary L. Gadbury, Lilian Golzarri-Arroyo, Richard J. Holden, Yasaman Jamshidi-Naeini, Doug Landsittel, Tapan Mehta, J. Michael Oakes, Arthur H. Owora, Greg Pavela, Javier Rojo, Michael W. Sandel, Daniel L. Smith, Colby J. Vorland, Pengcheng Xun, Roger Zoh, David B. Allison
Journal: Nature Aging (2022)
Social feasibility assessments in conservation translocations
Authors: Thomas R. Dando, Sarah L. Crowley, Richard P. Young, Stephen P. Carter, Robbie A. McDonald
Journal: Trends in Ecology & Evolution (2022)

Improving the effectiveness of conservation translocations could contribute to reversing global biodiversity loss. Although evaluations of ecological factors affecting translocation outcomes are commonplace, consideration of human social factors remains rare, hindering improvements to this conservation practice. We analysed 550 translocation case studies to explore the inclusion of social factors in project feasibility assessments. Reviewed projects often failed to assess social feasibility, and assessments, where attempted, tended to be narrow in scope. Consequently, challenges such as proactively addressing conflict often remained unaddressed. Insufficient knowledge sharing and prioritisation of ecological feasibility, to the detriment of social feasibility, remain barriers to effective planning. Successful outcomes of translocations are linked to early assessment of social feasibility and to the establishment of long-term commitments between people, places, and partners.
The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Overview of Challenges and Opportunities in Revising the Nodal Classification of Lung Cancer
Authors: Raymond Uyiosa Osarogiagbon, Paul Van Schil, Dorothy J. Giroux, Eric Lim, Paul Martin Putora, Yolande Lievens, Giuseppe Cardillo, Hong Kwan Kim, Gaetano Rocco, Andrea Bille, Helmut Prosch, Francisco Suárez Vásquez, Katherine K. Nishimura, Frank Detterbeck, Ramon Rami-Porta, Valerie W. Rusch, Hisao Asamura, James Huang
Journal: Journal of Thoracic Oncology (2022)
Adenovirus-Associated Uveitis with Necrotizing Retinitis
Authors: Sunao Sugita, Yoshihiko Usui, Hidemi Watanabe, Laura Panto, Miyabi Iida, Keisuke Suginoshita, Kanako O. Koyanagi, Akihiro Nishida, Yasuo Kurimoto, Masayo Takahashi, Tatsuya Shindo, Hiroaki Nishioka, Masahiko Takano, Takeshi Kezuka, Hiroshi Goto, Nobuyoshi Kitaichi
Journal: Ophthalmology (2022)
Suturing Olympics: A team-based approach to encouraging and assessing suturing competencies among dermatology residents
Authors: Rachel Rigo, Mario Maruthur, Cindy Parra, Haoming Xu, Kalee Shah, Erica H. Lee, Anthony Rossi, Kishwer S. Nehal, Kira Minkis
Journal: Journal of the American Academy of Dermatology (2022)
Orthogonal representations for robust context-dependent task performance in brains and neural networks
Authors: Timo Flesch, Keno Juechems, Tsvetomira Dumbalska, Andrew Saxe, Christopher Summerfield
Journal: Neuron (2022)

(Neuron 110, 1258–1270.e1–e11; April 6, 2022) We thank the authors of Mante et al. (2013) for alerting us to a labeling error in the presentation of our reanalysis of their data. Unfortunately, we switched the labels for "colour" and "motion" in Figures 4 and 6 as well as Figures S4 and S5, which provoked a discrepancy with the findings presented in the original report. The figures have now been corrected online. We apologize for any confusion this may have caused.Figure 4. Task representations in human fMRI and macaque unit recordings (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 6. Neural network and NHP data in support of gating theory (corrected)View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 6. Neural network and NHP data in support of gating theory (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure S4. Control analyses on the human fMRI and NHP datasets (corrected)View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure S4. Control analyses on the human fMRI and NHP datasets (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure S5. Gating in MLPs, NHPs and RNN model (corrected)View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure S5. Gating in MLPs, NHPs and RNN model (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Orthogonal representations for robust context-dependent task performance in brains and neural networksFlesch et al.NeuronJanuary 26, 2022In BriefHow do brains represent multiple tasks? The authors use artificial neural networks to derive a computational theory of neural coding and validate its predictions in recordings of human and macaque brains. The findings suggest that task-specific information is represented along orthogonal coding axes, which minimizes interference and maximizes robustness to noise. Full-Text PDF Open Access
Augmented-Dose Unilateral Recession-Resection Procedure in Acute Acquired Comitant Esotropia
Authors: Yulian Zhou, Ling Ling, Xiying Wang, Chao Jiang, Wen Wen, Chen Zhao
Journal: Ophthalmology (2022)

To compare the surgical amount of unilateral medial rectus recession and lateral rectus resection (RR) in patients with acute acquired comitant esotropia (AACE) versus common forms of esotropia and to provide dose-response reference for surgical planning in AACE.Retrospective study.Consecutive patients who underwent unilateral RR for AACE or common forms of esotropia correction from January 2018 to January 2022. Only patients who achieved motor and sensory success with a minimum follow-up of 3 months were analyzed.Group differences in the amount of medial rectus (MR) recession and lateral rectus (LR) resection were analyzed using multivariate regression models. Surgical dose responses in AACE were analyzed using multivariable regression models. Regression models were performed with and without adjustment for clinical confounders. Piecewise analysis was used to detect segmented results.Group difference in surgical amount and dose responses of unilateral RR in AACE.Fifty-four patients with AACE and 98 patients with common forms of esotropia were included. To correct comparable deviations, surgical amount performed was significant larger in AACE patients, with the adjusted group differences of 0.49 mm (95% confidence interval [CI], 0.34-0.65 mm; P < 0.001) in MR recession and 1.68 mm (95% CI, 1.25-2.11 mm; P < 0.001) in LR resection in patients with deviation < 40 prism diopters (Δ) and with a group difference of 1.22 mm (95% CI, 0.76-1.68 mm; P < 0.001) in LR resection in those with deviation ≥ 40 Δ. In AACE patients, in the adjusted model taking into account the intercept, dose responses of MR recession and LR resection in patients with deviation < 30 Δ were 5.11 Δ/mm (95% CI, 0.98-9.23 Δ/mm; P = 0.02) and 2.51 Δ/mm (95% CI, 0.57-4.45 Δ/mm; P = 0.02), respectively, and for those with deviation ≥ 30 Δ, the dose response of additional LR resection was 5.48 Δ/mm (95% CI, 4.56-6.40 Δ/mm; P < 0.001) to correct remaining deviation beyond 30 Δ.These findings provide quantitative evidence that augmented-dose unilateral RR should be performed in AACE for favorable surgical outcomes. The new surgical dose calculation proposed provides reference for surgical planning.The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Skin TARC/CCL17 increase precedes the development of childhood atopic dermatitis
Authors: Anne-Sofie Halling, Maria Rasmussen Rinnov, Iben Frier Ruge, Trine Gerner, Nina Haarup Ravn, Mette Hjorslev Knudgaard, Simon Trautner, Nikolai Loft, Lone Skov, Simon F. Thomsen, Alexander Egeberg, Emma Guttman-Yassky, Aske L.L. Rosted, Troels Petersen, Ivone Jakasa, Sanja Kezic, Jacob P. Thyssen
Journal: Journal of Allergy and Clinical Immunology (2022)

It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk.This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life.This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD.The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection.This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD.
Machine learning does not outperform traditional statistical modelling for kidney allograft failure prediction
Authors: Agathe Truchot, Marc Raynaud, Nassim Kamar, Maarten Naesens, Christophe Legendre, Michel Delahousse, Olivier Thaunat, Matthias Buchler, Marta Crespo, Kamilla Linhares, Babak J. Orandi, Enver Akalin, Gervacio Soler Pujol, Helio Tedesco Silva, Gaurav Gupta, Dorry L. Segev, Xavier Jouven, Andrew J. Bentall, Mark D. Stegall, Carmen Lefaucheur, Olivier Aubert, Alexandre Loupy
Journal: Kidney International (2022)
Database Commons: A Catalog of Worldwide Biological Databases
Authors: Lina Ma, Dong Zou, Lin Liu, Huma Shireen, Amir A. Abbasi, Alex Bateman, Jingfa Xiao, Wenming Zhao, Yiming Bao, Zhang Zhang
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Biological databases serve as a global fundamental infrastructure for the worldwide scientific community, which dramatically aid the transformation of big data into knowledge discovery and drive significant innovations in a wide range of research fields. Given the rapid data production, biological databases continue to increase in size and importance. To build a catalog of worldwide biological databases, we curate a total of 5825 biological databases from 8931 publications, which are geographically distributed in 72 countries/regions and developed by 1975 institutions (as of September 20, 2022). We further devise a z-index, a novel index to characterize the scientific impact of a database, and rank all these biological databases as well as their hosting institutions and countries in terms of citation and z-index. Consequently, we present a series of statistics and trends of worldwide biological databases, yielding a global perspective to better understand their status and impact for life and health sciences. An up-to-date catalog of worldwide biological databases, as well as their curated meta-information and derived statistics, is publicly available at Database Commons (https://ngdc.cncb.ac.cn/databasecommons/).
Monitoring Patients With Eosinophilic Esophagitis in Routine Clinical Practice - International Expert Recommendations
Authors: Ulrike von Arnim, Luc Biedermann, Seema S Aceves, Peter A Bonis, Margaret H Collins, Evan S Dellon, Glenn T Furuta, Nirmala Gonsalves, Sandeep Gupta, Ikuo Hirano, Alfredo J Lucendo, Stephan Miehlke, Salvatore Oliva, Christoph Schlag, Alain Schoepfer, Alex Straumann, Michael Vieth, Albert J Bredenoord
Journal: Clinical Gastroenterology and Hepatology (2022)
Anti-Tumor Necrosis Factor Treatment Does Not Decrease the Risk of Type 2 Diabetes in Patients With Inflammatory Bowel Disease
Authors: Marie Villumsen, Gry Poulsen, Nynne Nyboe Andersen, Mikael Andersson, Tine Jess, Kristine Højgaard Allin
Journal: Clinical Gastroenterology and Hepatology (2022)

Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are at increased risk of type 2 diabetes (T2D).1,2 The proinflammatory cytokine tumor necrosis factor α (TNF-α) plays a central role in the inflammatory process of IBD, and anti-TNF-α therapy is commonly used in the treatment of IBD. Because anti-TNF therapy is suggested to improve insulin sensitivity,3 we hypothesized that treatment with anti-TNF therapy decreases the risk of T2D in patients with IBD.
Quality of Surveillance Impacts the Colitis-Associated Advanced Neoplasia Risk: A Multicenter Case-Control Study
Authors: Maarten te Groen, Monica Derks, Nathan den Broeder, Charlotte Peters, Gerard Dijkstra, Annemarie de Vries, Tessa Romkens, Carmen Horjus, Nanne de Boer, Michiel de Jong, Iris Nagtegaal, Lauranne Derikx, Frank Hoentjen
Journal: Clinical Gastroenterology and Hepatology (2022)

Although colorectal cancer (CRC) surveillance is embedded in clinical inflammatory bowel disease (IBD) practice, a subset of patients still develops advanced neoplasia (AN) (high-grade dysplasia [HGD] and/or CRC). We aimed to assess the impact of surveillance quality on AN risk in IBD.
RGD density along with substrate stiffness regulate hPSC hepatocyte functionality through YAP signalling
Authors: Samuel J.I. Blackford, Tracy T.L. Yu, Michael D.A. Norman, Adam M. Syanda, Michail Manolakakis, Dariusz Lachowski, Ziqian Yan, Yunzhe Guo, Elena Garitta, Federica Riccio, Geraldine M. Jowett, Soon Seng Ng, Santiago Vernia, Armando E. del Río Hernández, Eileen Gentleman, S. Tamir Rashid
Journal: Biomaterials (2022)

Human pluripotent stem cell-derived hepatocytes (hPSC-Heps) may be suitable for treating liver diseases, but differentiation protocols often fail to yield adult-like cells. We hypothesised that replicating healthy liver niche biochemical and biophysical cues would produce hepatocytes with desired metabolic functionality. Using 2D synthetic hydrogels which independently control mechanical properties and biochemical cues, we found that culturing hPSC-Heps on surfaces matching the stiffness of fibrotic liver tissue upregulated expression of genes for RGD-binding integrins, and increased expression of YAP/TAZ and their transcriptional targets. Alternatively, culture on soft, healthy liver-like substrates drove increases in cytochrome p450 activity and ureagenesis. Knockdown of ITGB1 or reducing RGD-motif-containing peptide concentration in stiff hydrogels reduced YAP activity and improved metabolic functionality; however, on soft substrates, reducing RGD concentration had the opposite effect. Furthermore, targeting YAP activity with verteporfin or forskolin increased cytochrome p450 activity, with forskolin dramatically enhancing urea synthesis. hPSC-Heps could also be successfully encapsulated within RGD peptide-containing hydrogels without negatively impacting hepatic functionality, and compared to 2D cultures, 3D cultured hPSC-Heps secreted significantly less fetal liver-associated alpha-fetoprotein, suggesting furthered differentiation. Our platform overcomes technical hurdles in replicating the liver niche, and allowed us to identify a role for YAP/TAZ-mediated mechanosensing in hPSC-Hep differentiation.
TREM2 dependent and independent functions of microglia in Alzheimer’s disease
Authors: Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna
Journal: Molecular Neurodegeneration (2022)

Abstract Microglia are central players in brain innate immunity and have been the subject of extensive research in Alzheimer’s disease (AD). In this review, we aim to summarize the genetic and functional discoveries that have advanced our understanding of microglia reactivity to AD pathology. Given the heightened AD risk posed by rare variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2), we will focus on the studies addressing the impact of this receptor on microglia responses to amyloid plaques, tauopathy and demyelination pathologies in mouse and human. Finally, we will discuss the implications of recent discoveries on microglia and TREM2 biology on potential therapeutic strategies for AD.
Covid-19: Molnupiravir does not cut hospital admissions or deaths in vaccinated people at high risk, trial finds
Authors: Jacqui Wise
Journal: BMJ (2022)

Covid-19: Molnupiravir does not cut hospital admissions or deaths in vaccinated people at high risk, trial finds Jacqui WiseThe antiviral drug molnupiravir does not reduce hospital admissions or deaths among vaccinated high risk patients with covid-19 infection, show the results of a landmark trial that included more than 25 000 participants. 1 However, the oral treatment was associated with reduced viral detection and load, and patients recovered around four days more quickly than those who received usual care.The Panoramic study, now peer reviewed and published in the Lancet, was first available as a preprint in October. 2 In November 2021 the UK was the first country to authorise Merck Sharp & Dohme's molnupiravir (Lagevrio) for the treatment of mild to moderate covid-19 in adults with at least one risk factor for severe illness.The government bought 2.23 million doses at an estimated cost of £1bn, and the then health secretary Sajid Javid called it a "gamechanger for the most vulnerable and the immunosuppressed." 3 4 However, the government was criticised for overhyping the antiviral drug in official press releases.